Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0015672 (fatigue)
51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-one HIV negative Japanese patients with chronic hepatitis C who had congenital bleeding disorders, 15 hemophilia A, 3 hemophilia B, 1 von Willebrand's disease, 1 afibrinogenemia and 1 thrombasthenia, were treated with 9 million units 3 times a week of natural interferon (IFN)-alpha for 6 months. They were followed, biochemically and virologically, for at least 18 months after therapy discontinuation to evaluate the long-term results. Liver biopsy, hepatitis C virus (HCV) genotyping and quantification of viral load by polymerase chain reaction (PCR) were performed to identify the predictors of a favorable response to IFN treatment. One male patient with hemophilia A dropped out because of general fatigue and was excluded from evaluation. Ten (50.0%) patients continued to be HCV RNA negative in serum together with normal ALT levels throughout the study. Subtype 1b and a high level of viremia significantly associated with an unfavorable outcome on the response to IFN although liver histology was not definitive for predicting the response. We concluded that a 6-month treatment with high doses of natural IFN-alpha was effective in inducing a long-term response without relapse of viremia in 50% of chronic hepatitis C patients with congenital bleeding disorders and that HCV subtype and pretreatment level of viremia were useful predictors of the response to IFN in treating such patients.
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PMID:A long-term follow-up study of interferon treatment for chronic hepatitis C in Japanese patients with congenital bleeding disorders. 885 94

Therapy with ribavirin for 6-12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000-1200 mg of ribavirin daily for 24 months. Serum aminotransferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects.
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PMID:Prolonged therapy of chronic hepatitis C with ribavirin. 891 4

We studied the morbidity of chronic hepatitis C in patients referred to a tertiary care medical facility. The medical records of 500 consecutive cases of chronic hepatitis C were examined for the following: (1) source and time of exposure, (2) signs and symptoms of liver disease, (3) degree of alcohol intake, (4) liver biopsy findings, (5) extrahepatic disease manifestations, and (6) coexisting illnesses that could have an impact on morbidity. Morbidity and histologic findings were evaluated in relation to the duration of hepatitis C. The onset of infection could be determined in 376 patients (75%). A close relationship between the length of infection and disease features was not observed. Fatigue was common at all stages of infection. Whereas cirrhosis occurred more frequently in patients with disease of long duration, 15-24% of patients had signs of advanced liver disease (ascites, encephalopathy, thrombocytopenia) within six years of exposure. Overt extrahepatic manifestations of chronic hepatitis C occurred infrequently, and depression was reported in 24% of untreated patients. In conclusion, in patients referred to a tertiary care setting, chronic hepatitis C is often associated with significant morbidity.
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PMID:Morbidity of chronic hepatitis C as seen in a tertiary care medical center. 900 36

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.
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PMID:Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. 925 61

Alpha interferons have been used widely to treat chronic hepatitis C virus infection. These include recombinant interferons, purified natural leukocyte, and lymphoblastoid interferons. Alpha interferon is administered by subcutaneous or intramuscular injection either daily or three times weekly for a period of 6 to as long as 24 months. A wide array of adverse effects of alpha interferon have been described. Several side effects such as fever, headache fatigue, arthralgias, and myalgias are common, especially with the initial injections. These early side effects of interferon are predictable and are encountered in the majority of patients. These may not require dose modification, but can be problematic for a significant proportion of patients. Other adverse events effects may require dose modification or even discontinuation of therapy in 2% to 10% of patients. Neuropsychiatric side effects such as depression and irritability can be most troublesome; their mechanisms are not well understood. Granulocytes, platelets, and red blood cell counts decrease during treatment, but the decreases are usually mild, although they can be dose limiting if cell counts are low initially. Interferon has important immunomodulatory properties, and treatment can induce autoimmune phenomena, the most frequent being autoimmune thyroiditis with either hypothyroidism or hyperthyroidism, especially in predisposed patients. Other autoimmune disease can be aggravated by interferon therapy. Severe and even life-threatening side effects of interferon occur in 0.1% to 1% of patients; these include thyroid, visual, auditory, renal, and cardiac impairment, and pulmonary interstitial fibrosis. Some of these side effects may be irreversible. Higher doses of interferon (above 5 million units three times weekly) cause higher rates of adverse events than standard doses. Contraindications to alpha interferon have been recognized.
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PMID:Side effects of alpha interferon in chronic hepatitis C. 930 75

The effects of interferon-alpha (IFN-alpha), given at a dosage of 6 MU thrice weekly for 12 months, on gonadal function were investigated in 18 males affected by chronic hepatitis C. Periodically, all patients were clinically monitored and questioned about sexual function. Gonadotropin and serum androgen concentrations (follicle-stimulating hormone, luteinizing hormone, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin) were tested every 3 months. Ten of 18 patients (55%) responded to IFN-alpha therapy. Serum total testosterone and sex hormone binding globulin values decreased slightly at the third month of treatment, then returned to baseline values. Serum free testosterone and other sex hormones remained essentially unchanged during IFN-alpha therapy. Four patients (22.2%) complained of sexual dysfunction (impaired libido, erectile failure, and impaired ejaculation), which was unrelated to any significant hormonal change and resolved after IFN therapy was stopped. Serum sex hormones values did not differ between responders and nonresponders to IFN-alpha. This study indicates that 12 months treatment with 6 MU of IFN-alpha thrice weekly does not significantly affect gonadal function in men with chronic hepatitis C. The sexual dysfunction observed could be ascribed to such other side effects of IFN as asthenia, fatigue, or anxiety, or it could have a psychologic basis.
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PMID:Long-term interferon-alpha therapy does not affect sex hormones in males with chronic hepatitis C. 933 29

Virus-associated hemophagocytic syndrome (VAHS) is associated with a systemic viral infection and is mainly observed in immunosuppressed adult patients. This rare disease is characterized by symptoms which include a high fever, pancytopenia, and splenomegaly and sometimes results in a fatal outcome. However, thus far, little has been reported on VAHS in general surgical patients. We herein report this rare complication which occurred in a patient with hepatocellular carcinoma, as well as chronic hepatitis C, after a hepatic resection. A 66-year-old man with chronic hepatitis C and recurrent hepatocellular carcinoma underwent a repeat hepatic resection without any blood transfusions. In the early postoperative period, he recovered uneventfully. However, he suddenly began to suffer from a high fever (38.4 degrees C) and severe pancytopenia 8 days after surgery. Activated macrophages, which phagocytosed erythrocytes, were identified by a cytological study of the bone marrow. The patient was therefore treated with methylprednisolone pulse therapy 13 days after surgery. On the day following the initial administration of methylprednisolone, his clinical condition drastically improved. Fortunately, with methylprednisolone therapy, our patient recovered from acute, severe pancytopenia. In general surgery, it is often difficult for surgeons to use steroids due to their negative side effects. However, when symptoms such as fever, general fatigue and pancytopenia are observed, even in posthepatectomy patients with hepatocellular carcinoma and hepatitis, a bone marrow aspiration should be performed as soon as possible, and when VAHS is suspected, steroid pulse therapy should be the first treatment of choice. This rare but sometimes fatal complication should thus be taken into consideration in the postoperative management of hepatectomized patients with chronic hepatitis C.
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PMID:Virus-associated hemophagocytic syndrome after hepatic resection: a case report. 949 16

A 42-year-old male type A hemophiliae who been using coagulates since 1971 was diagnosed Human Immunodeficiency Virus (HIV) positive in 1993. Medical history included liver disfunction in 1987, with chronic hepatitis C (CHC) diagnosed in 1989. He was admitted to the hospital in October, 1994 because of general fatigue. Serum transaminase was elevated, CD4 was 221/micro L, and CD8 was 990. CD4/CD8 ratio was 0.2. HCV was of genotype 2b and 10(6) copies/50 microL, 8 week-Interferon (IFN)-beta treatment was started. HCV RNA was eliminated by week 8 and was sustained for one year with no severe side effects. With careful patient screening, IFN therapy for CHC with HIV may be an effective treatment.
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PMID:[A case of report--interferon therapy is useful for chronic hepatitis C with human immunodeficiency virus infection]. 969 78

Autoimmune hepatitis is a rare chronic hepatitis of unknown etiology. Immunological changes are conspicuous, with tissue antibodies found in a high proportion of patients. There is a female preponderance of 2-3:1 and the disease often affects young people. The presenting symptoms are vague, fatigue being the most important general symptom. The diagnosis is often made at a late stage of the disease when symptoms of liver decompensation and cirrhosis are obvious. We present two cases of AIH in young women diagnosed at a late stage with advanced cirrhosis, for whom symptoms of liver disease had been intermittently present for 12 and 9 months, but wrongly attributed to presumed acute viral hepatitis acquired on holiday in the Mediterranean. In order not to miss the diagnosis, it is important to confirm suspected viral hepatitis serologically, to look for liver disease stigmata in patients with abnormal liver enzymes, and to be especially aware of the possibility of AIH in young women with concommittant or family history of other autoimmune diseases.
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PMID:[Autoimmune hepatitis--a rare cause of elevated transaminases]. 988 37

The coadministration of ribavirin with recombinant interferon alfa-2b (rIFN-alpha 2b) compared with rIFN-alpha 2b alone markedly enhanced sustained virologic response rates in relapsed and treatment-naive chronic hepatitis C patients. The potential for ribavirin to likewise exacerbate the adverse events associated with the alpha interferons is reviewed. The overall safety and tolerability of combination rIFN-alpha 2b/ribavirin therapy was evaluated in 2,089 patients treated in phase III clinical studies conducted in the United States and internationally. Serious adverse events were also evaluated on an interim basis in > 25,000 patients--a majority of whom were treated with combination therapy (open label)--treated worldwide in investigator-initiated studies. Patients in the phase III studies received 3 million International Units rIFN-alpha 2b three times per week by subcutaneous injection plus either ribavirin or placebo orally in divided daily doses of 1,000 or 1,200 mg for patients weighing < or = 75 or > 75 kg, respectively. Adverse event frequency and severity and dose modifications were recorded throughout the 24-week (relapse) or 48-week (naive) treatment period and 24-week follow-up period. Clinically significant adverse events included anemia and depression. There was no evidence that the adverse effects of alpha interferon (e.g., fatigue, depression, neutropenia) were exacerbated by ribavirin. Severe adverse events were limited due to strict adherence to dose-modification criteria; approximately 6% to 9% of patients discontinued combination therapy because of an adverse event. Clinically serious adverse events, dose reductions and discontinuations, and potential mechanisms of toxicity associated with rIFN-alpha 2b and ribavirin are examined.
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PMID:Safety of combination interferon alfa-2b/ribavirin therapy in chronic hepatitis C-relapsed and treatment-naive patients. 1034 94


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